Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones

High consumption of soybean and soybean-related products is hypothesized to contribute to protection against breast cancer. Soybean is a rich source o f genistein, a putative cancer chemopreventive agent. Fermented soy milk (F SM), which is made of soy milk fermented with the Bifidobacterium breve str ain Yakult, contains larger amounts of the isoflavone aglycones genistein a nd daidzein than unfermented soy milk. In the present study, we examined th e effects of FSM and its component isoflavone mixture (genistein:daidzein 4 :1) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mamma ry carcinogenesis in rats. Starting at 7 weeks of age, female Sprague-Dawle y rats mere given PhIP at a dose of 85 mg/ kg body wt by intragastric admin istration four times a week for 2 weeks. They mere fed control high fat bas al diet or experimental high fat diet containing 10% FSM or 0.02 or 0.04% i soflavone mixture during and after carcinogen exposure. The incidences (per centage of rats with tumors) of mammary gland tumors were 71% in the contro l diet group, 51% in the FSM group and 68 and 61% in the groups treated wit h isoflavone mixture at 0.02 and 0.04%, respectively. Mammary tumor multipl icities (number of tumors per rat) mere 1.2 +/- 0.2 for 10% FSM, 2.2 +/- 0. 4 for 0.02% isoflavone mixture and 1.5 +/- 0.3 for 0.04% isoflavone mixture , being clearly smaller than the control diet value (2.6 +/- 0.5). Furtherm ore, feeding of FSM and the isoflavone mixture at both doses reduced the si zes of mammary tumors. Since the amounts of isoflavones in 10% FSM are appr oximately equivalent to those in the 0.02% isoflavone mixture, the chemopre ventive activity of FSM could be partly attributable to the presence of iso flavones such as genistein and daidzein.